Alpha1‐ and alpha2‐adrenoreceptor antagonists produce opposing mydriatic effects by a central action

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Abstract
In anaesthetized rats, intravenous administration of alpha2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) and raulwolscine (0.3-3.0 mg kg-1) produced a dose-related inhibition of sciatic nerve-(ScN) mediated reflex pupillary dilation (parasympatho-inhibition). The rank order of potency was idazoxan > yohimbine > rauwolscine. Under similar experimental conditions, intravenous administration of alpha1-adrenoreceptor antagonists prazosin (0.03-1.0 mg kg-1), phenoxybenzamine (0.3-3.0 mg kg-1) and corynanthine (0.03-1.0 mg kg-1) produced a dose-dependent potentiation of the reflex mydriasis with the potency order being prazosin > corynanthine > phenoxybenzamine. Intravenous yohimbine (1.5 mg kg-1) reversed the potentiation caused by the alpha1-adrenoreceptor antagonists and blocked the reflex mydriasis. Parasympatho-inhibition and mydriasis elicited by hypothalamic stimulation was not affected by the alpha2-adrenoreceptor antagonists yohimbine (0.3-3.0 mg kg-1), idazoxan (0.03-0.3 mg kg-1) or the alpha1-adrenoreceptor antagonist prazosin (0.3-1.0 mg kg-1). Microinjection of prazosin (3-30 ng) into the oculomotor nuclear complex (IIIn), produced a dose-related potentiation, whereas microinjection of yohimbine (0.3-3.0 .mu.g) produced a dose-related blockade of reflex mydriasis. The above findings support the hypothesis that ascending mechanisms (e.g. afferent ScN) produce inhibition of parasympathetic oculomotor tone to the iris by activation of central postsynaptic alpha2-adsrenoreceptors. Furthermore, these studies demonstrate that alpha2-adrenoreceptor antagonists block and alpha1-adrenoreceptor antagonists potentiate the reflex mydriasis. These actions appear to be localized within the pupilloconstrictor regions of the brain (oculomotor nuclear complex).